Description:
The primary purpose of this study is to determine: the recommended Phase 2 doses (RP2Ds) of
JNJ-64264681 and JNJ 67856633 when administered together in participants with B cell
non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) (Part A - Dose Escalation);
and the safety of the RP2Ds for this combination in different histologies/participant
populations (Part B - Cohort Expansion).
Title
- Brief Title: A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia
- Official Title: A Phase 1b, Open-Label Study of the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-64264681 in Combination With JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia
Clinical Trial IDs
- ORG STUDY ID:
CR108877
- SECONDARY ID:
2020-003149-12
- SECONDARY ID:
64264681LYM1002
- NCT ID:
NCT04657224
Conditions
- Lymphoma, Non-Hodgkin
- Chronic Lymphocytic Leukemia
Interventions
| Drug | Synonyms | Arms |
|---|
| JNJ-64264681 | | Part A: Dose escalation: JNJ-64264681 and JNJ-67856633 |
| JNJ-67856633 | | Part A: Dose escalation: JNJ-64264681 and JNJ-67856633 |
Purpose
The primary purpose of this study is to determine: the recommended Phase 2 doses (RP2Ds) of
JNJ-64264681 and JNJ 67856633 when administered together in participants with B cell
non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) (Part A - Dose Escalation);
and the safety of the RP2Ds for this combination in different histologies/participant
populations (Part B - Cohort Expansion).
Detailed Description
Bruton's tyrosine kinase (BTK) is a cytoplasmic tyrosine kinase that plays a critical role in
B cell activation via the B cell receptor (BCR) signaling pathway. BTK is important for
normal B-cell activation and the pathophysiology of B cell malignancies. A few BTK inhibitors
have demonstrated clinical activity in non-Hodgkin lymphoma (NHL) and chronic lymphocytic
leukemia (CLL). Non-Hodgkin lymphoma represents a diverse set of diseases, of which more than
60 subtypes have been identified and classified by the world health organization.
JNJ-64264681 is a second-generation, orally active, selective, and irreversible covalent
inhibitor of BTK and JNJ-67856633 is an orally bioavailable, potent, and selective first in
class mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) inhibitor
that binds to an allosteric site on MALT1 with a mixed-type mechanism. JNJ-64264681 and
JNJ-67856633 inhibit BTK and MALT1, respectively, and both BTK and MALT1 are involved in
transmitting the pro-survival BCR signal. The study will consist of Screening Phase (28
days); Treatment Phase (from Cycle 1 Day 1 up to end of treatment, each cycle is a 21-day
cycle) and a Follow-up Phase (from end of treatment visit until lost to follow-up, withdrawal
of consent, death, 6 months after start of first subsequent antineoplastic therapy). The
total study duration is estimated at 2 years and 2 months. Safety assessments will include
physical examinations, vital signs, electrocardiograms, clinical safety laboratory
assessments, eastern cooperative oncology group performance status, echocardiogram, and
adverse events monitoring.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Part A: Dose escalation: JNJ-64264681 and JNJ-67856633 | Experimental | Participants will receive JNJ-64264681 and JNJ-67856633 will be administered together until disease progression, intolerable toxicity, withdrawal of consent, or the investigator. | |
| Part B: Cohort Expansion: JNJ-64264681 and JNJ-67856633 | Experimental | Participants will receive JNJ-64264681 and JNJ-67856633 at the recommended Phase 2 dose (RP2D) determined in Part 1. | |
Eligibility Criteria
Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
- Cardiac parameters within the following range: corrected QT interval (QTcF) <= 480
milliseconds
- Participants with B cell non-Hodgkin lymphoma (NHL) must have tumor tissue available
at baseline as described in the protocol. This is not required for participants with
chronic lymphocytic leukemia (CLL)
- Women of childbearing potential must agree to use a barrier method of contraception;
use a highly effective preferably user-independent method of contraception; not to
donate eggs (ova, oocytes) or freeze them for future use for the purposes of assisted
reproduction during the study; not to plan to become pregnant; and not to breast-feed
Exclusion Criteria:
- Part A and select cohorts in Part B: Prior treatment with JNJ 64264681 or
JNJ-67856633. Previously discontinued treatment with a Bruton's tyrosine kinase (BTK)
or mucosa-associated lymphoid tissue lymphoma translocation protein (MALT) inhibitor
other than JNJ 64264681 or JNJ-67856633 due to participant or doctor choice without
evidence of progression or intolerable class-related toxicity will be eligible
- Known (active) central nervous system (CNS) involvement
- Received prior solid organ transplantation
- Participant has known allergies, hypersensitivity, or intolerance to JNJ-64264681 or
JNJ 67856633 or excipients
- Toxicities from previous anti-cancer therapies that have not resolved to baseline
levels, or to Grade less than (<) 2 (except for alopecia [>=Grade 2], vitiligo [Grade
2] and peripheral neuropathy [Grade 1])
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Part A: Number of Participants with Dose-limiting Toxicity (DLT) |
| Time Frame: | Up to 28 days |
| Safety Issue: | |
| Description: | Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity. |
Secondary Outcome Measures
| Measure: | Plasma Concentrations of JNJ-64264681 and JNJ-67856633 |
| Time Frame: | Up to 2 years and 3 months |
| Safety Issue: | |
| Description: | Plasma concentrations of JNJ-64264681 and JNJ-67856633 will be assessed. |
| Measure: | Bruton's Tyrosine Kinase (BTK) Occupancy in Peripheral Blood Mononuclear Cell (PBMCs) |
| Time Frame: | Up to 2 years and 3 months |
| Safety Issue: | |
| Description: | BTK occupancy will be assessed. |
| Measure: | Overall Response Rate (ORR) |
| Time Frame: | Up to 2 years and 3 months |
| Safety Issue: | |
| Description: | ORR is defined according to Non-Hodgkin Lymphoma, International Workshop on Chronic Lymphocytic Leukemia (iwCLL); and Response assessment in Waldenström Macroglobulinemia (IWWM). |
| Measure: | Time to First Response |
| Time Frame: | Up to 2 years and 3 months |
| Safety Issue: | |
| Description: | Time to first response defined for the responders as the time from the date of first dose of study treatment to the date of initial documentation of a first response as defined in the disease-specific response criteria. |
| Measure: | Duration of Response |
| Time Frame: | Up to 2 years and 3 months |
| Safety Issue: | |
| Description: | DOR will be calculated from the date of initial documentation of a response to the date of first documented evidence of relapse, as defined in the disease-specific response criteria, or death due to any cause, whichever occurs first. |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Janssen Research & Development, LLC |
Last Updated
August 13, 2021
